Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 4660 | 14203;14204;14205 | chr2:178739255;178739254;178739253 | chr2:179603982;179603981;179603980 |
| N2AB | 4343 | 13252;13253;13254 | chr2:178739255;178739254;178739253 | chr2:179603982;179603981;179603980 |
| N2A | None | None | chr2:None | chr2:None |
| N2B | 4297 | 13114;13115;13116 | chr2:178739255;178739254;178739253 | chr2:179603982;179603981;179603980 |
| Novex-1 | 4422 | 13489;13490;13491 | chr2:178739255;178739254;178739253 | chr2:179603982;179603981;179603980 |
| Novex-2 | 4489 | 13690;13691;13692 | chr2:178739255;178739254;178739253 | chr2:179603982;179603981;179603980 |
| Novex-3 | None | None | chr2:None | chr2:None |
Information
Reported SAVs
| SNV | RS | DUET |
PolyPhen-2 |
Condel |
Rhapsody |
REVEL |
MVP |
Source |
MAF |
Disease |
Zygosity |
Site annotation |
mCSM PPI |
Predicted PPI site |
Comments |
AFR |
AMR |
AMS |
ASJ |
EAS |
EUR |
FIN |
MDE |
NFE |
SAS |
OTH |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/K | rs754231728  |
None | 0.608 | D | 0.584 | 0.442 | None | gnomAD-4.0.0 | 6.8739E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.03251E-07 | 0 | 0 |
| T/M | rs754231728 |
-0.129 | 0.328 | D | 0.556 | 0.382 | None | gnomAD-2.1.1 | 2.16E-05 | None | None | None | None | N | None | 8.28E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.15E-05 | 0 |
| T/M | rs754231728 |
-0.129 | 0.328 | D | 0.556 | 0.382 | None | gnomAD-3.1.2 | 3.94E-05 | None | None | None | None | N | None | 9.65E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| T/M | rs754231728 |
-0.129 | 0.328 | D | 0.556 | 0.382 | None | gnomAD-4.0.0 | 9.95679E-06 | None | None | None | None | N | None | 6.68717E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 9.36062E-06 | 0 | 0 |
Saturation Mutagenesis
SAV |
AlphaMissense (IC) |
AlphaMissense Class (IC) |
AlphaMissense (N2AB) |
AlphaMissense Class (N2AB) |
mCSM |
mCSM class |
PolyPhen-2 |
PolyPhen-2 Class |
Rhapsody |
Rhapsody Class |
Condel |
Condel Score |
Site annotation |
mCSM PPI |
Predicted PPI site |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.118 | likely_benign | 0.1231 | benign | -1.087 | Destabilizing | 0.201 | N | 0.583 | neutral | D | 0.597896772 | None | None | N |
| T/C | 0.416 | ambiguous | 0.4271 | ambiguous | -0.773 | Destabilizing | 0.992 | D | 0.656 | neutral | None | None | None | None | N |
| T/D | 0.5255 | ambiguous | 0.5616 | ambiguous | -1.767 | Destabilizing | 0.617 | D | 0.589 | neutral | None | None | None | None | N |
| T/E | 0.3149 | likely_benign | 0.3338 | benign | -1.543 | Destabilizing | 0.447 | N | 0.586 | neutral | None | None | None | None | N |
| T/F | 0.2833 | likely_benign | 0.2995 | benign | -0.669 | Destabilizing | 0.85 | D | 0.701 | prob.neutral | None | None | None | None | N |
| T/G | 0.3736 | ambiguous | 0.4105 | ambiguous | -1.519 | Destabilizing | 0.617 | D | 0.635 | neutral | None | None | None | None | N |
| T/H | 0.2298 | likely_benign | 0.2369 | benign | -1.693 | Destabilizing | 0.977 | D | 0.707 | prob.neutral | None | None | None | None | N |
| T/I | 0.1742 | likely_benign | 0.1825 | benign | 0.055 | Stabilizing | 0.739 | D | 0.625 | neutral | None | None | None | None | N |
| T/K | 0.1733 | likely_benign | 0.1847 | benign | -0.531 | Destabilizing | 0.608 | D | 0.584 | neutral | D | 0.590934058 | None | None | N |
| T/L | 0.1192 | likely_benign | 0.1341 | benign | 0.055 | Stabilizing | 0.217 | N | 0.609 | neutral | None | None | None | None | N |
| T/M | 0.0963 | likely_benign | 0.097 | benign | -0.017 | Destabilizing | 0.328 | N | 0.556 | neutral | D | 0.730289887 | None | None | N |
| T/N | 0.1909 | likely_benign | 0.2035 | benign | -1.331 | Destabilizing | 0.617 | D | 0.593 | neutral | None | None | None | None | N |
| T/P | 0.7547 | likely_pathogenic | 0.8284 | pathogenic | -0.294 | Destabilizing | 0.896 | D | 0.637 | neutral | D | 0.729581935 | None | None | N |
| T/Q | 0.209 | likely_benign | 0.2117 | benign | -1.013 | Destabilizing | 0.048 | N | 0.519 | neutral | None | None | None | None | N |
| T/R | 0.1361 | likely_benign | 0.1442 | benign | -0.864 | Destabilizing | 0.845 | D | 0.625 | neutral | D | 0.576363604 | None | None | N |
| T/S | 0.1297 | likely_benign | 0.1362 | benign | -1.478 | Destabilizing | 0.016 | N | 0.356 | neutral | N | 0.516008546 | None | None | N |
| T/V | 0.1514 | likely_benign | 0.1585 | benign | -0.294 | Destabilizing | 0.447 | N | 0.621 | neutral | None | None | None | None | N |
| T/W | 0.6245 | likely_pathogenic | 0.6352 | pathogenic | -0.945 | Destabilizing | 0.992 | D | 0.728 | prob.delet. | None | None | None | None | N |
| T/Y | 0.2963 | likely_benign | 0.306 | benign | -0.525 | Destabilizing | 0.92 | D | 0.699 | prob.neutral | None | None | None | None | N |
Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.